Immunoglobulins
On this page
Direct answer
Immunoglobulins are Y-shaped proteins built from two heavy and two light chains held by disulphide bonds, with the Fab arms binding antigen and the Fc stem fixing complement, binding cell receptors or crossing the placenta. The five classes differ in their heavy chains and therefore in function: IgG opsonises and crosses the placenta, IgM appears first and fixes complement best, secretory IgA guards mucosae, IgE triggers allergy, and IgD sits on naive B cells. Almost every viva question on this topic reduces to matching a class with one of these jobs.
What you must remember
- Basic unit: two heavy plus two light chains; light chains are kappa (about 60 per cent) or lambda; papain yields two Fab and one Fc, pepsin yields one F(ab')2.
- IgG: 75–80 per cent of serum Ig, only class to cross the placenta, half-life about 23 days (longest), four subclasses, opsonises and activates classical complement.
- IgM: pentamer with a J chain, about 970 kDa (largest), first antibody formed in primary response, most efficient complement fixer, never crosses the placenta — raised levels mean recent infection.
- IgA: dimer with J chain and secretory component; the predominant immunoglobulin in colostrum, saliva, tears and gut secretions; protects mucosal surfaces.
- IgE: heat-labile, binds Fc receptors on mast cells and basophils, mediates anaphylaxis and anti-parasite immunity; least abundant class.
- IgD: trace serum levels; functions as the antigen receptor on naive B lymphocytes.
- Multiple myeloma produces a monoclonal spike (M-band), IgG most often; Bence Jones proteins are monoclonal free light chains in urine.
- ABO blood group antibodies are naturally occurring IgM (do not cross the placenta), which is why ABO haemolytic disease of the newborn is mild; Rh antibodies are IgG (cross the placenta), which is why Rh disease is severe.
Working through a real interpretation
A 62-year-old man presents with bone pain, fatigue and a normocytic anaemia with a very high ESR. Total protein is 11 g/dL with albumin only 3 g/dL — the globulin fraction has ballooned. Cellulose acetate electrophoresis shows a dense, narrow band in the gamma region, and immunofixation types it as IgG kappa. Urine heated in the laboratory clouds at 40–60 degrees Celsius and clears again on boiling: Bence Jones proteinuria, present in over half of myeloma patients because excess light chains spill into urine. Contrast this with a child with recurrent pyogenic sinopulmonary infections: here the entire gamma fraction is flat, suggesting combined antibody deficiency, and quantification may show absent IgG with low IgM — agammaglobulinaemia — for which lifelong immunoglobulin replacement is the treatment. The same electrophoresis read differently in chronic liver disease or tuberculosis gives a broad, polyclonal swelling of gamma globulins: many clones responding at once, never a single spike.
Where students slip
The classic error is attaching placental transfer to IgM "because it is the biggest and first". Size is exactly why it cannot cross — the pentamer is far too large, and placental transfer is an active, Fc-mediated process unique to IgG, peaking in the third trimester. This single fact explains why maternal IgG protects the newborn for the first three to six months, why preterm infants are more vulnerable, and why active immunisation of the mother (tetanus, pertussis) protects the baby. A second slip: saying "IgA fixes complement". It does not, in the classical pathway; its role is mucosal immune exclusion, which is why selective IgA deficiency, the commonest primary immunodeficiency, causes recurrent mucosal infections while serum complement pathways remain intact.
Frequently asked questions
Which immunoglobulin crosses the placenta and why?
IgG, via an Fc-mediated active transport across the placenta. No other class is transferred, which is why maternal IgG is the newborn's main antibody protection during the first months of life.
How do papain and pepsin fragments of immunoglobulin differ?
Papain cleaves above the hinge to give two separate Fab fragments (each monovalent, antigen-binding but no precipitation) and one Fc. Pepsin cuts below the hinge to give a single divalent F(ab')2 that still cross-links antigen, plus degraded Fc fragments.
What are Bence Jones proteins and how are they detected?
Monoclonal free light chains produced by plasma cell clones in multiple myeloma. They show characteristic heat behaviour — precipitating around 40–60 degrees Celsius and redissolving on boiling — though modern practice uses urine protein electrophoresis and serum free light chain assays.
Why is IgM the first antibody produced but IgG the one that protects later?
IgM is expressed earliest during B cell development and needs no class switching, so it dominates the primary response; upon repeat antigen exposure, class switching and affinity maturation convert the response to high-affinity IgG and IgA.
Which immunoglobulin is highest in secretions and what stabilises it there?
Secretory IgA, a dimer joined by a J chain and protected from proteolysis by the secretory component supplied by epithelial cells. It is the principal antibody in colostrum, giving breastfed infants mucosal passive immunity.